Does the Initial Treatment of the Primary Tumor Impact Prognosis after Recurrence in Locally Advanced Rectal Cancer? Results From A Retrospective Cohort Analysis

Introduction: Role of neoadjuvant therapy (NAT) for local advanced rectal cancer (LARC) has been well proved, but its impact on patients who relapse remains unknown. This study aims to delineate the influence of initial treatment and MRI-defined risk factors on post recurrent survival in recurrent LARC patients. Patients and methods: LARC patients who underwent radical surgery and subsequently developed recurrence were retrospectively identified. Patients were stratified based on MRI-defined local risk assessment and the initial treatment modality for the primary tumor (NAT or primary surgery). They were classified into four groups: high-risk LARC with NAT (HiN), high-risk LARC with primary surgery (HiS), low-risk LARC with NAT (LoN), and low-risk LARC with primary surgery (LoS). The primary endpoint was survival after recurrence. Result 381 cases of relapsed patients were identified from 2,329 LARC patients. Salvage surgery was performed on 33.1% of these patients. Patients with single-site recurrence or who underwent salvage surgery exhibited significantly prolonged survival time after recurrence ( P  < 0.001). Patients in the HiS group showed poorer survival after recurrence compared to the other three subgroups ( P  = 0.034). This subset of patients, characterized by receiving less adjuvant treatment after primary surgery, had a shorter recurrence interval compared to the other groups ( P  = 0.001). Conclusions Our findings reaffirm the prognostic significance of salvage surgery in relapsed patients from a LARC cohort. Moreover, MRI defined high-risk LARC patients who received upfront surgery without NAT had shorter interval to recurrence and poorer survival outcome after recurrence. Our result underscore the critical role of NAT in improving patients’ survival after recurrence. Trial registration: Supplementary registration was carried out at clinicaltrials.gov (Registration number: NCT06314737) on March 14, 2024. The study was retrospectively registered.